JP7729972B2 - Capillary array window holder related systems and methods - Google Patents

Description

The present invention generally relates to a capillary array window holder configured to hold a parallel arrangement of capillaries, particularly the window portions of such capillaries. The present invention also relates to devices, assemblies, and systems including such holders, as well as methods utilizing such holders. Capillaries can be used to contain samples to be measured by optical-based instruments (e.g., instruments that measure fluorescence or absorbance). Capillaries can be used, for example, in capillary electrophoresis (CE).

BACKGROUND Analytical instruments often utilize capillaries (i.e., tubes with bores on the micrometer scale) to contain and transport sample-containing fluids (in either liquid or gas phase) for various purposes. In some analytical instruments, the capillary (or at least an optically transparent portion of the capillary, called the capillary window) can be used as a sample detection cell. In this case, the analytical instrument is configured to perform optical measurements (e.g., fluorescence, absorbance, imaging, etc.) of sample analytes (i.e., sample components of interest, such as chemical compounds or biological compounds) contained in the capillary by reading electromagnetic energy emitted from the sample. Such emissions may be in response to the sample being illuminated by a beam of electromagnetic energy sent to the capillary window by a light source in the analytical instrument. In some analytical instruments, the capillary may contain a separation medium tailored to separate different analytes of the sample based on different properties or attributes, such as molecular size, molecular configuration, charge, etc. In some analytical techniques, the separation medium may be stationary (i.e., stationary phase) within the capillary window. In this case, the sample is carried by a fluid (i.e., mobile phase) through the capillary and contacts the separation medium. As the sample migrates through the separation medium, different analytes of the sample are separated from one another, thereby facilitating their detection/measurement by an analytical instrument. Examples of analytical separation techniques include capillary electrophoresis (CE, particularly capillary gel electrophoresis or CGE), liquid chromatography (LC), and gas chromatography (GC).

Sample analysis may be enhanced by operating multiple capillary windows in parallel, with each capillary window housing an individual sample. In this case, the analytical instrument may be configured to simultaneously read or even irradiate multiple capillary windows. In this case, compact packaging of the capillaries is advantageous to enable high magnification of the capillaries with a camera installed in the analytical instrument. When analytical separations such as CE are being performed, compact packaging allows for higher resolution and sensitivity of the detected separation. However, once the spacing between capillaries reaches a certain compactness, such as 1.5 mm or less, crosstalk effects between adjacent capillaries occur, adversely affecting the background of the detection/imaging signal acquired by the analytical instrument. This can lead to target sample mismatch and/or inaccurate representation of sample concentration. Most commercially available analytical instruments that utilize parallel arrays of capillary windows (e.g., 96 capillaries) are adversely affected by crosstalk-related problems because the capillary windows are spaced very closely (e.g., 0.025 mm) so that the analytical instrument can map all of the capillaries with reasonable magnification. When using a smaller number of parallel capillaries (e.g., 12 spaced approximately 1.5 mm apart), an artificially large field of view is required to make the effects of crosstalk insignificant. This artificially limits the magnification of the capillaries at the camera or detector utilized by the analytical instrument, and consequently limits the resolution and sensitivity of the acquired data. When applications require high excitation intensities, the capillaries must be closely spaced to ensure sufficiently high illumination, which causes significant crosstalk that significantly increases background noise in the detected signal.

There is a continuing need to provide capillary arrays that overcome problems associated with crosstalk effects.

SUMMARY To address, in whole or in part, the above-mentioned problems and/or other problems that may be appreciated by those skilled in the art, the present disclosure provides methods, processes, systems, apparatus, instruments, and/or devices, as illustrated by way of example in the implementations described below.

For example, the present disclosure provides a capillary array window holder including a plurality of capillary channels. The present disclosure further provides a capillary array assembly including a capillary array window holder and a plurality of capillaries disposed in the individual capillary channels. At least a portion of each capillary channel is open. The capillaries include individual windows, i.e., portions of the capillaries are not covered by an outer coating, thereby allowing transmission of electromagnetic radiation into and out of the windows. The capillaries are mounted in the capillary channels such that the windows are located in the open channels. The open channels, and thus the windows, are exposed to electromagnetic radiation (e.g., excitation light as described herein) on at least one side of the capillary array window holder. The exposed side can also be used to detect electromagnetic radiation emitted from or detectable at the windows (e.g., emission light as described herein). Alternatively, two opposing sides (e.g., top and bottom) of the capillary array window holder, at least where the open channels and thus the windows are located, can be exposed to electromagnetic radiation. This latter configuration can be useful, for example, to illuminate the open channels (and thus the windows) on one side and detect electromagnetic radiation emitted from or detectable by the windows on the other side. Adjacent open channels are separated from each other by window bars. The window bars block line-of-sight between adjacent windows to reduce or eliminate crosstalk between adjacent capillaries when performing optical measurements on the samples. A capillary array assembly as described herein can be mounted (or attached, docked, coupled, etc.) to a sample analysis system configured to perform optical measurements on samples in the capillaries. In one non-exclusive example, the sample analysis system can be configured to perform capillary electrophoresis on the samples.

According to one example, a capillary array window holder includes a first end portion; a second end portion; and a window portion disposed along a longitudinal axis between the first end portion and the second end portion, the window portion including a plurality of window bars extending along the longitudinal axis and spaced apart from one another along a transverse axis perpendicular to the longitudinal axis; the window bars defining a plurality of parallel open channels configured to respectively accommodate a plurality of capillaries, the window bars being made of an opaque material such that the window bars block line of sight along the transverse axis between adjacent open channels, the open channels being exposed at an upper side of the window portion to allow transmission of light to and from the open channels at the upper side.

According to another example, a capillary array assembly includes a capillary array window holder according to any of the examples disclosed herein; and a plurality of capillaries, each positioned in a respective one of the capillary channels such that the window of each capillary is positioned in a respective open channel.

According to another example, a capillary array assembly includes a plurality of capillary array window holders according to any of the examples disclosed herein; and a plurality of capillaries, each capillary positioned in a respective one of the capillary channels in each capillary array window holder such that the window of each capillary is positioned in a respective open channel.

According to another example, a sample analysis system includes a capillary array assembly according to any of the examples disclosed herein; and a photodetector positioned in optical alignment with the open channel.

According to another example, a method for analyzing a sample includes providing a capillary array assembly according to any of the examples disclosed herein; and performing optical measurements of each detectable sample in the window to obtain optical data from one or more analytes of the sample.

Other devices, apparatus, systems, methods, features, and advantages of the present invention will be or become apparent to one with skill in the art upon examination of the following drawings and detailed description. All such additional systems, methods, features, and advantages are intended to be included within this description, be within the scope of the present invention, and be protected by the accompanying claims.

The present invention may be better understood by referring to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. In the drawings, like reference characters indicate corresponding parts throughout the different views.

FIG. 1 is a top perspective view of one non-exclusive example of a capillary array assembly according to the present disclosure.

FIG. 2 is a bottom perspective view of the capillary array assembly shown in FIG. 1.

FIG. 2 is a plan view of the capillary array assembly shown in FIG. 1.

2 is an elevational view of a first end of the capillary array assembly shown in FIG. 1. FIG.

2 is an elevational view of a second end of the capillary array assembly shown in FIG. 1. FIG.

2 is a cross-sectional elevation view of a portion of the central section of the capillary array assembly shown in FIG. 1.

FIG. 10 is a top perspective view of another example of a capillary array assembly according to the present disclosure.

FIG. 10 is a cross-sectional elevation view of another example of a portion of a central section of a capillary array assembly according to the present disclosure.

FIG. 10 is a plan view of another example of a capillary array assembly according to the present disclosure.

FIG. 10 is a perspective view of a capillary array window holder of the capillary array assembly shown in FIG. 9.

FIG. 10 is a top perspective view of another example of a capillary array assembly according to the present disclosure.

FIG. 12 is a top exploded perspective view of the capillary array assembly shown in FIG. 11.

FIG. 10 is a top perspective view of another example of a capillary window holder according to the present disclosure.

FIG. 14 is a plan view of the capillary window holder shown in FIG. 13.

15 is a longitudinal side view of another example of a capillary array assembly according to the present disclosure, including the capillary array window holder shown in FIGS. 13 and 14. FIG.

1 is a schematic diagram of an example of a sample analysis system (or apparatus, analytical instrument, etc.) including a capillary array assembly according to any of the examples described herein.

DETAILED DESCRIPTION FIGS. 1-6 illustrate one non-exclusive example of a capillary array assembly 100 according to the present disclosure. FIGS. 1 and 2 are top and bottom perspective views of the capillary array assembly 100. For reference and explanation purposes, FIG. 1 includes an arbitrarily positioned Cartesian coordinate (x-y-z) frame. The x-axis, y-axis, and z-axis are also referred to herein as the longitudinal (vertical) axis (or capillary axis), horizontal axis, and height axis, respectively. Dimensions along the x-axis, y-axis, and z-axis are interpreted as length, width, and height, respectively. The y-z plane is also referred to herein as the front (cross-section). In this example, the capillary array assembly 100 extends along the longitudinal axis (x-axis). In this example, the top view of FIG. 3 is the x-y plane. The end (elevation) views of FIGS. 4 and 5 and the cross-sectional view of FIG. 6 are in the y-z plane (front).

The capillary array assembly 100 includes a capillary array window holder 104 and a plurality of capillaries 108. The capillary array window holder 104 is configured to securely hold the capillaries 108 in a parallel configuration such that the capillaries 108 are spaced apart from one another along a horizontal axis and are held in place and at a fixed distance from one another. To this end, the capillary array window holder 104 includes a plurality of capillary channels, described below. Each capillary 108 is disposed in a respective one of the capillary channels. In the illustrated example, twelve capillaries 108 are provided in the twelve capillary channels, although the capillary array assembly 100 may include any number of capillary channels and a corresponding number of capillaries 108.

The capillary array window holder 104 is defined by a body of material. The body may be monolithic or may include two or more components attached or secured together. Depending on the embodiment, the entire capillary array window holder 104, or at least certain portions of the body (described below), are opaque to light. Within the context of this disclosure, an "opaque" material (or "black" material) is a material that is effective for blocking electromagnetic energy propagating within a specific range of wavelengths, for example, by absorbing and/or reflecting such energy. Within the context of this disclosure, the term "light" refers to electromagnetic energy (i.e., photons) in a general sense and thus does not limit electromagnetic energy to the visible range. Depending on the embodiment, the desired wavelength range to be blocked may be within the ultraviolet range, the visible range, the infrared range, or a combination or overlap of two or more of these ranges. In the context of the present disclosure, the ultraviolet region is understood to extend from 10 nm to 400 nm, the visible region is understood to extend from 400 nanometers (nm) to 700 nm, and the infrared region is understood to extend from 700 nm to 1000 nm (1 millimeter (mm)), recognizing that these regions may differ slightly and/or overlap slightly depending on the technical basis involved. In one non-exclusive example, the opaque material is opaque to light propagating in wavelengths within the range of 190 nm to 800 nm.

Examples of opaque (or black) materials for the body of the capillary array window holder 104 include, but are not limited to, various metals (e.g., aluminum, nickel, copper, etc.), various metal alloys, silicon, ceramic, glass, and polymers (engineering plastics (e.g., polyoxymethylene (POM), liquid crystal polymer (LCP), polyacrylamide (PA), polycarbonate (PC), polymethyl methacrylate (PMMA), polyether ether ketone (PEEK), polyethylene (PE), etc.)). Depending on its composition, the material may need to be treated to render it opaque (black) as part of the manufacturing process, as will be recognized by those skilled in the art. In the case of metals or metal alloys, for example, the material (or at least its outer surface) may be rendered opaque by suitable anodizing, plating, or oxidation techniques.

In general, any technique appropriate for the material utilized (e.g., organic polymer, metal, semi-metal, etc.) can be utilized to fabricate/manufacture the capillary array window holder 104. The particular fabrication technique implemented should be well suited to forming the high aspect ratio window bars described herein with high-precision dimensions and geometries, where at least one of the dimensions (height and/or width) is on the micrometer scale. For polymers, example fabrication techniques include, but are not limited to, micro-injection molding and 3D printing. For metals or semi-metals, various additive, subtractive, and formative manufacturing techniques can be utilized. Examples of additive techniques include, but are not limited to, 3D printing (e.g., lithography-based metal manufacturing (LMM)), electroplating, electroforming or electroplating, chemical vapor deposition (CVD), and physical vapor deposition (PVD). Examples of subtractive techniques include, but are not limited to, dry etching (e.g., plasma-based etching, including reactive ion etching (RIE) and deep reactive ion etching (DRIE)), wet etching (i.e., chemical etching, for example, using hydrofluoric acid or other acids) followed by diffusion bonding, micromachining, micromilling, microlaser machining, and micro-electrical discharge machining (EDM). Examples of formative techniques include, but are not limited to, microstamping, microembossing, and LIGA (German: photolithography (Lithographie), electrolytic plating (Galvanoformung), forming (Abformung)).

In the illustrated example, the capillary array window holder 104 (i.e., its body) generally includes a top side 112 and a bottom side 116 in the x-y plane, a first end 120, and a second end 124 axially opposite the first end 120 along the longitudinal axis (x-axis). In the context of the present disclosure, the terms "top" and "bottom" are used in relation to one another only to distinguish them from one another and are not intended to limit the capillary array assembly 100 to any particular positional relationship relative to the ground or any other reference datum. The capillary array window holder 104 (i.e., its body) also includes a first end portion 128 terminating at the first end 120, a second end portion 132 terminating at the second end 124, and a window portion 136. In this example, the window portion 136 is disposed along the longitudinal axis between the first end portion 128 and the second end portion 132 , and may also be referred to as the central portion. In this example, the largest dimension of the capillary array window holder 104 is its longitudinal dimension (its length). However, in other examples, the largest dimension of the capillary array window holder is not necessarily its longitudinal dimension.

The first end portion 128 includes a first upper wall 140 on the upper side 112, and the second end portion 132 includes a second upper wall 144 on the upper side 112. The first upper wall 140 covers a portion of the capillary 108 passing through the first end portion 128, and the second upper wall 144 covers a portion of the capillary 108 passing through the second end portion 132. The first upper wall 140 and the second upper wall 144 may be made of an opaque material as described above. Thus, the first upper wall 140 and the second upper wall 144 prevent light from being transmitted through the upper side 112 to or from the capillaries 108 in the first end portion 128 and the second end portion 132. In other words, the first upper wall 140 and the second upper wall 144 block any line of sight to or from the capillary 108 in a direction to or from the upper side 112.

In another embodiment, the first and second top walls 140, 144 may not be part of the body of the capillary array window holder 104 itself. Instead, the first and second top walls 140, 144 may be part of an instrument console to which the capillary array assembly 100 will be docked for operation, or may be part of a cartridge to which the capillary array assembly 100 will be mounted, which can then be docked to the instrument console.

In this example, each capillary 108 comprises a tube made of an optically transparent material. In the context of this disclosure, a "transparent" material is a material that allows the transmission of light propagating at wavelengths within a range that includes (at least) the wavelength(s) of the excitation light EX and emission light EM (discussed further below) utilized in the application of the capillary array assembly 100. Depending on the embodiment, the excitation light EX and/or emission light EM may be ultraviolet light, visible light, or infrared light. Examples of tube materials include, but are not limited to, silica, fused silica, fused quartz, doped (synthetic) fused silica, and polymers such as polytetrafluoroethylene (PTFE) (e.g., for UV detection). A portion of each capillary 108 (e.g., a majority of the length of each capillary 108) is coated, i.e., circumferentially surrounded by a coating. The coating serves to protect the tube from damage or destruction and also serves to prevent the transmission of light to and from the tube. Examples of such coating materials include, but are not limited to, polyimide (PI), acrylate, silicone, and fluoropolymer. Meanwhile, at least a portion of each capillary 108 is bare (i.e., uncoated) so that the transparent tube is exposed to ambient light and thus light. Thus, each capillary 108 includes a bare (or exposed or uncoated) portion, referred to herein as a capillary window 148, and coated portions (hereinafter referred to as coated portions) 152 on either side (along the longitudinal axis) of the capillary window 148. As an example, the capillary 108 may be fabricated by first forming a tube, then coating the entire length of the tube, and stripping the coating from portions of the capillary 108 to form the capillary window 148, all of which may be done by any suitable technique now known or later developed.

In contrast to the first end portion 128 and the second end portion 132, the window portion 136 does not include an upper wall on the upper side 112. That is, the window portion 136 is open (or has an opening) on the upper side 112, thereby exposing the capillaries 108 (particularly, the portions of the capillaries 108 that pass through the window portion 136, i.e., the capillary window 148) to the surrounding space on the upper side 112. The capillaries 108 are attached to the capillary array window holder 104 so that the capillary windows 148 are aligned parallel to one another (in front (cross section)) and positioned in the window portion 136. Thus, the capillary windows 148 are exposed to light on the upper side 112 through the opening in the window portion 136. With this configuration, the window portion 136 defines an excitation (or combined excitation/detection) region of the capillary array assembly 100. In one example, the opening length of the window portion 136 is in the range of 500 μm to 4 mm.

In some examples, the window portion 136 may be covered by a transparent wall or transparent cover (not shown, but see FIGS. 11 and 12 ), which may be configured to protect and/or assist in securing the position of the capillary in the capillary array window holder 104. That is, at least a portion of the top wall or cover located directly above the capillary window 148 is transparent. Depending on the embodiment, such a transparent wall may be considered to be part of the capillary array assembly 100, or part of the instrument console to which the capillary array assembly 100 will be docked for operation, or part of the cartridge to which the capillary array assembly 100 will be attached as described above.

In one example, the length of the capillary window 148 is greater than the length of the opening in the window portion 136. In this case, the first upper wall 140 of the first end portion 128 and the second upper wall 144 of the second end portion 132 cover the portion of the capillary window 148 extending below the first upper wall 140 and the second upper wall 144, as well as the covering portion 152 immediately adjacent to the capillary window 148/window portion 136. The first upper wall 140 and the second upper wall 144 thus provide an additional means for blocking the transmission of light to and from the capillary 108. In particular, in an analytical instrument configured to measure fluorescence emitted from an analyte within the capillary 108, the first upper wall 140 and the second upper wall 144 prevent the covering portion 152 from being exposed to light, such as excitation light EX, thereby preventing or inhibiting the emission of fluorescence from the covering portion 152. This is particularly advantageous when the coating material itself fluoresces or emits fluorescence in response to the excitation light EX. The fluorescence signal produced by the coating material can be detected by the analytical instrument and, as a result, contributes to undesirable noise (or background signal) in the acquired optical measurements. However, in this example, the first upper wall 140 and the second upper wall 144 prevent such unwanted fluorescence from reaching the detector (or camera) of the analytical instrument.

In the context of the present disclosure, excitation light EX may refer to a beam of light (or light rays) transmitted from a light source external to the capillary array assembly 100 to the capillaries 108 at the window portion 136 (i.e., capillary window 148) to irradiate the sample present in the individual capillaries 108. The beam of excitation light EX may be coherent or incoherent, depending on the embodiment. Such a light source may be part of an analytical instrument configured to perform optical measurements on analytes in the sample to determine properties or attributes (e.g., the concentration of one or more analytes) and/or to obtain microscopic images, etc. Emission light EM may refer to light emitted from each capillary 108 (i.e., each capillary window 148) in response to incident excitation light EX, which may be received by a detector (or camera) of the analytical instrument.

In some examples, excitation light EX may be used to illuminate the sample in capillary 108 to measure absorbance (or transmittance) and/or acquire a microscopic image. In other examples, excitation light EX of a selected wavelength may be used to "excite" a target analyte in the sample in capillary 108 by inducing fluorescence emission (e.g., from an inherently fluorescent analyte or from a fluorophore added or bound to the analyte). For convenience, the term "excitation" is used herein to refer to all such cases, including illumination that does not involve fluorescence emission. In examples of acquiring images, emission light EM is light emitted from capillary 108 within the camera's field of view, which is processed as needed to construct an image of the sample in the capillary illuminated by excitation light EX. In examples of measuring absorbance (or transmittance), the emission light EM emitted from capillary 108 is attenuated due to partial absorbance of the excitation light EX by the sample in capillary 108. In such cases, the emission light EM may be of the same wavelength as the excitation light EX. In the example of measuring fluorescence, the emission light EM is light emitted from the test substance in response to the wavelength of the excitation light EX. In such cases, the emission light EM is of a different wavelength than the excitation light EX. Another example is fluorescence microscopy, where the captured image is based in part on fluorescent emission. For convenience, the term "emission" is used herein to refer to all such cases, including non-fluorescent transmission.

The window portion 136 further includes a plurality of window bars (or central bars) 156 arranged parallel to and spaced apart from one another along the lateral axis. In this example, the window bars 156 are elongated along the longitudinal axis and generally extend along the length of the window portion 136 from the first end portion 128 to the second end portion 132. The window bars 156 are aligned parallel to and interdigitated with the capillaries 108 such that each capillary 108 is flanked on both sides by a respective window bar 156 along the lateral axis. Thus, each capillary 108 (particularly the capillary window 148 in the window portion 136) is physically separated from adjacent capillaries 108 on either side by the intervening window bars 156. The window bars 156 are made of an opaque material as described above and thus function as an optical shield as further described below.

2, in this example, the window portion 136 further includes a bottom wall 260 located on the bottom side 116 of the capillary array window holder 104. The bottom wall 260 may extend across the entire window portion 136 to cover the portions of the capillaries 108 that pass through the window portion 136 (i.e., the capillary window 148). The window bar 156 extends upward from the bottom wall 260 and may be in contact with or integral with the bottom wall 260. In particular, if the capillary array window holder 104 is formed as a monolithic body, the bottom wall 260 may be made of the same opaque material as the other components of the capillary array window holder 104 described herein. Depending on the embodiment, the opaque material may be desired or required to prevent light from being transmitted into or out of the capillaries 108 in the window portion 136 via the bottom side 116.

The bottom wall 260 may be provided in applications where both excitation and detection are performed on the same side of the capillary assembly 100 (e.g., the top side 112, as shown schematically by the EX and EM beams in FIG. 1). Depending on the embodiment of the analytical instrument and the type of optical measurement technique implemented thereby, the angle between the EX and EM beams may range, for example, from 0 to 65 degrees. In other embodiments, the capillary array assembly 100 may be configured to transmit light from the top side 112 to the bottom side 116 through the capillaries 108, in which case the bottom wall 260 is not provided, as will be described further below in connection with other embodiments.

In the example shown in FIG. 2 , the first end portion 128 and the second end portion 132 do not include bottom walls. Instead, the first top wall 140 and the second top wall 144 may serve as the primary structural members of the first end portion 128 and the second end portion 132. Coating the capillaries 108 at the first end portion 128 and the second end portion 132 may provide adequate optical shielding for the bottom side 116, particularly when the capillary array assembly 100 is mounted in a housing (e.g., an interior portion of an analytical instrument) that optically shields the bottom side 116. However, in other examples, the first end portion 128 and/or the second end portion 132 may include a bottom wall.

4 is an elevational view of the first end 120 of the capillary array assembly 100, particularly showing the first end portion 128. In this example, the first end portion 128 includes a plurality of first end channels 464 extending along the longitudinal axis and spaced apart from one another along the transverse axis. The first end channels 464 are configured to hold or accommodate individual capillaries 108. The first end channels 464 are cooperatively defined by the first upper wall 140 and a plurality of first inner surfaces. In particular, each first end channel 464 is cooperatively defined by the lower surface (inner surface) of the first upper wall 140 and one of the plurality of first inner surfaces (according to the cross-sectional shape or contour of the first end channel 464). The first end channels 464 are "closed" channels in the sense that they are completely enclosed by the structure of the first end portion 128, specifically, covered by the first top wall 140. In the illustrated example, the first end channels 464 have a rectilinear (e.g., rectangular or square) cross section in front (cross section). In this case, each first end channel 464 is defined by the underside of the first top wall 140 and three first inner surfaces: two side inner surfaces 468A and 468B (in the x-z plane) joined by a bottom inner surface 472 (in the x-y plane).

The first end portion 128 further includes a plurality of first end bars (or dividers) 466 elongated along the longitudinal axis. The first end bars 466 are aligned with corresponding window bars 156 of the window portion 136 and may be integral with or be extensions of the window bars 156. In this example, each first end bar 466 includes a lateral inner surface 468A of one first end channel 464 and an adjacent lateral inner surface 468B of an adjacent first end channel 464. Similar to the window bars 156 of the window portion 136, the first end bars 466 are aligned parallel to and interdigitated with the capillaries 108 such that each capillary 108 is physically separated from adjacent capillaries 108 on either side by the intervening first end bar 466.

5 is an elevational view of the second end 124 of the capillary array assembly 100, particularly showing the second end portion 132. The configuration of the second end portion 132 may be the same as or similar to the configuration of the first end portion 128. Accordingly, the second end portion 132 includes a plurality of axially elongated second end channels 570 configured to hold or accommodate individual capillaries 108. In this example, the second end channels 570 are cooperatively defined by two lateral inner surfaces 568A and 568B joined by the second top wall 144 and a plurality of first inner surfaces, particularly the bottom inner surface 572. The second end portion 132 further includes a plurality of axially elongated second end bars (or dividers) 574, each of which includes the lateral inner surface 568A of one of the second end channels 570 and the adjacent lateral inner surface 568B of the adjacent second end channel 570. The second end bars 574 are aligned with corresponding window bars 156 of the window portion 136 and may be integral with or be extensions of the window bars 156. Similar to the window bars 156 and the first end bar 466, the second end bars 574 are aligned parallel to and interdigitated with the capillaries 108 such that each capillary 108 is physically separated from adjacent capillaries 108 on either side by the intervening second end bar 574.

The capillary 108 may be secured in place within the first end channel 464 and/or the second end channel 570 by any suitable means. For example, a resin or other adhesive may be utilized.

6 is a cross-sectional elevation view of a portion of the window portion 136. The window bar 156 extends along the longitudinal axis between the corresponding first end bar 466 of the first end portion 128 and the second end bar 574 of the second end portion 132. The window portion 136 includes a plurality of open channels 678 extending along the longitudinal axis and spaced apart from one another along the transverse axis. Each open channel 678 holds or accommodates an individual one of the capillaries 108, specifically a capillary window 148. The open channels 678 are defined by the window bars 156. Each window bar 156 is positioned between two adjacent open channels 678, thus physically separating the capillary windows 148 present in those open channels 678. In this example, open channels 678 are also defined by the bottom wall 260 (particularly the exposed upper surface of the bottom wall 260) underlying the central portion 136. The open channels 678 are "open" in the sense that they are exposed to at least one side (in this example, the top side 112) of the capillary array window holder 104, thereby allowing light to be transmitted to and from the capillary window 148 via that side (top side 112).

Thus, the capillary channels of the capillary array window holder 104 are defined at least by the window portion 136, and particularly by the open channel 678 of the window portion 136. In this example, the capillary channels are cooperatively defined by the first end portion 128, the second end portion 132, and the window portion 136. In particular, each capillary channel includes one of the open channels 678 aligned along the longitudinal axis with a corresponding one of the first end channels 464 and a corresponding one of the second end channels 570. In accordance with one aspect of the present disclosure, the capillary channels are configured (e.g., sized and positioned to block a line of sight) between adjacent capillaries 108 in a direction along the transverse axis. In particular, the window bar 156 is configured to block a line of sight along the transverse axis between adjacent capillary windows 148. With this configuration, the capillary array window holder 104 may significantly reduce (or even eliminate) crosstalk between adjacent capillary windows 148 (inter-capillary crosstalk).

In the example shown in FIG. 6 , each window bar 156 includes (or is bounded by) an inner lateral surface 668A that at least partially defines one open channel 678, an inner lateral surface 668B that at least partially defines an adjacent open channel 678, and a top surface 676 (in the x-y plane) that joins the two inner lateral surfaces 668A and 668B. Each window bar 156 has a bar width W along a horizontal axis corresponding to the top surface 676 and a bar height H along a height axis corresponding to the inner lateral surfaces 668A and 668B. Thus, each window bar 156 has a cross-section at the front defined by the bar width W and the bar height H. To facilitate blocking line-of-sight between the capillary windows 148 (and thus reducing or eliminating crosstalk), the bar height H is at least equal to, and typically is at least slightly greater than, the outer capillary diameter D of the capillary windows 148. Typically, the capillary outer diameter D is on the scale of micrometers (μm), i.e., less than 1 millimeter (mm). In one example, the capillary outer diameter D is in the range of 25 μm to 250 μm, or 90 μm to 200 μm (one particular example is 192 μm), in which case the bar height H is at least in the range of 25 μm to 250 μm, or 90 μm to 200 μm, or greater than 250 μm. In one example, the bar height H is greater than the capillary outer diameter D by an amount in the range of 5 μm to 25 μm. Typically, the bar width W is on the scale of micrometers. In one example, the bar width W is in the range of 25 μm to 1500 μm, or 25 μm to 100 μm.

The cross-sectional size (i.e., cross-sectional area) of each window bar 156 may be characterized by the bar aspect ratio A of the bar 156, defined herein as the ratio of bar height H to bar width W (A=H:W). As discussed above, in addition to affecting the ability of the window bar 156 to block line-of-sight between adjacent capillary windows 148, the bar aspect ratio A determines the pitch (or lateral spacing) of the open channels 678 and thus the capillary windows 148. This pitch, in turn, determines the density of capillaries 108 packed in the window portion 136 of the capillary array window holder 104, and thus the number of capillary windows 148 that can be read by the detection or imaging optics of an associated analytical instrument. In one example, the bar aspect ratio A is in the range of 1 to 10.

Because the high aspect ratio window bars 156 reduce crosstalk, they allow the capillary windows 148 to be arranged with a high degree of compactness without appreciably affecting the signal-to-noise ratio. Thus, the window bars 156 may reduce background noise and enable higher magnification and better resolution, sensitivity, and sample quantification by analytical instruments. Furthermore, the open channels 678 defined by the window bars 156 position the capillary windows 148 with high precision and in a well-defined manner, enabling highly accurate and reproducible docking and alignment with the optical components of the analytical instrument. Furthermore, the capillary array window holder 104 provides highly effective mechanical protection for the fragile capillaries 108.

In the examples described above, the cross-section of the capillary channel is configured as a straight line. However, the cross-section may have other types of shapes, such as other types of polygons or partially rounded shapes. In another example, a portion of the cross-section, particularly the bottom surface of the capillary channel, may be (partially) V-shaped, which may facilitate proper positioning of the capillaries 108 in the capillary channel. If the bottom surface is configured as (or includes) a V-shaped groove, such V-shaped geometry should not impair the ability of the capillary array window holder 104 to achieve a high packing density of the capillaries 108 while maintaining a bar of light shield between the capillaries 108, as disclosed herein.

The capillary array assembly 100 can be mounted on any suitable analytical instrument configured to perform optical measurements on analytes contained in the capillaries 108. Depending on the embodiment, the capillary array assembly 100 can be loaded directly into the console of the analytical instrument and aligned with the analytical instrument's optical system, or can be configured as part of a cassette that is loaded into the console. In the example shown in FIG. 1 , the capillary channels (and corresponding array of capillaries 108) are located in a capillary plane, and the capillary array window holder 104 includes one or more mounting mechanisms located in a mounting plane that is offset from the capillary plane along a height axis. In the illustrated example, the mounting mechanisms include a first mounting member 180 and a second mounting member 182 that can be part of or attached to the first end portion 128 and the second end portion 132, respectively. The first and second mounting members 180 and 182 may be secured to the instrument console (or secured to the cartridge, which is then secured to the instrument console) in any suitable manner. The first and second mounting members 180 and 182, or other portions of the capillary array window holder 104, may include other mounting mechanisms not shown, as well as mechanisms for precisely positioning and securing the capillaries 108, reference mechanisms for facilitating threading of the capillaries 108 into the capillary channels, mechanisms for facilitating optical alignment with the optical system of the analytical instrument, etc.

7 is a top perspective view of another example of a capillary array assembly 700 according to the present disclosure. The capillary array assembly 700 may have many features that are the same as or similar to the capillary array assembly 100 shown in FIG. 1. Accordingly, such features are indicated by the same reference numerals in FIG. 7. The capillary array assembly 700 differs primarily in that it has a greater number of capillaries 108 (96 capillaries 108 in this example). In one example, and as shown in FIG. 7, the capillary array assembly 100 has a modular configuration that allows several individual capillary array assemblies 100 (configured as described above) to be arranged in parallel, thereby providing a greater number of capillaries 108 as desired. In other words, the capillary array assembly 700 of FIG. 7 can be constructed from several capillary array assemblies 100, such as eight capillary array assemblies 100 in the illustrated example. In such cases, the smaller capillary array assembly 100 may be considered a module or portion (segment) of the larger capillary array assembly 700.

Figure 8 is a cross-sectional elevation view of another example of a capillary array assembly 800 according to the present disclosure. In particular, Figure 8 is a cross-sectional view of a portion of the window portion 836 of the capillary array assembly 800, including the window bar 856 and the open channel 878 containing the capillary window 148. The window portion 836 shown in Figure 8 can be compared to the window portion 136 of the capillary array assembly 100 shown in Figure 6. In this example, the window portion 836 does not have a bottom wall; instead, the open channel 878 is open on the bottom side 116 as well as on the top side 112. With this pass-through-illumination configuration, the capillary array assembly 800 allows the transmission of light through the window portion 836, as shown by the EX and EM beams in Figure 8. That is, in the through-illumination configuration, light can be transmitted through the window portion 836 to the top and bottom sides of the capillary array window holder of the capillary array assembly 800. In this case, the window bar 856 can be structurally supported by other portions of the capillary array assembly 800, such as the axial end portions of the window holder body of the capillary array assembly 800. In one example, such axial end portions are similar to the first end portion 128 and second end portion 132 described above in connection with FIGS. 1-5.

Figure 9 is a plan view of another example of a capillary array assembly 1100 according to the present disclosure. As in other embodiments, the capillary array assembly 1100 includes a capillary array window holder 1104 and a plurality of capillaries 108 each mounted in a parallel configuration in a capillary channel of the capillary array window holder 1104. Figure 10 is a perspective view of the capillary array window holder 1104 without any capillaries 108. In the illustrated example, twelve capillaries 108 are provided in twelve capillary channels, although the capillary array assembly 1100 may include any number of capillary channels and a corresponding number of capillaries 108.

As in other embodiments, the capillary array window holder 1104 (i.e., its body) generally includes a top side 1112 and a bottom side 1116 in the x-y plane, a first end 1120, and a second end 1124 axially opposite the first end 1120 along a longitudinal axis (x-axis). The capillary array window holder 1104 (i.e., its body) also includes a first end portion 1128 terminating at the first end 1120, a second end portion 1132 terminating at the second end 1124, and a window portion 1136 disposed along the longitudinal axis between the first end portion 1128 and the second end portion 1132.

The capillary channels are defined by individual open channels 1178 in the window portion 1136. The open channels 1178 are divided by axially elongated, opaque window bars 1156, as described above. In this example, the capillary channels are further defined by first end channels 1164 and second end channels 1170, where each open channel 1178 is axially disposed between the corresponding first end channel 1164 and second end channel 1170. The first end channel 1164 and second end channel 1170 are divided by the first end bar 1166 and second end bar 1174, respectively, as described above. The capillary channels are axially discontinuous in that each open channel 1178 is axially spaced from the corresponding first end channel 1164 on one side and from the corresponding second end channel 1170 on the other side.

In this example, the capillary array window holder 1104 (i.e., its body) further includes one or more bottom walls 1160 at the bottom side 1116 that underlie (thereby covering, at the bottom side 1116) the window portion 1136, or further includes a first end portion 1128 and/or a second end portion 1132. The bottom wall(s) may be opaque, i.e., made of an opaque material as described above. Thus, the capillary array assembly 1100 in this example has a same-side excitation/detection configuration, meaning that excitation light EX can be transmitted to the window portion 1136 at the top side 1112 and emission light EM can be transmitted from the window portion 1136, as described above in connection with FIG. 1 . To this end, the top side of the window portion 1136, or the entire top side of the capillary array assembly 1100, is open as shown. In one example, all or a portion of the capillary 108 may be covered by a top wall or cover (not shown), which may be configured to protect the capillary and/or help secure its position in the capillary array window holder 1104. At least a portion of such top wall covering (directly above) the capillary window 148 is transparent.

9 and 10, the capillary array window holder 1104 also includes mounting features 1180. In this example, the mounting features 1180 are located below the capillary channels and capillaries 108. In this example, the mounting features 1180 are semicircular recesses formed in the body (e.g., bottom wall 1160) of the capillary array window holder 1104. These mounting features 1180 can be brought into contact with complementary shaped mounting features (e.g., posts) on an underlying plate or other support structure (not shown). In other embodiments, the mounting features 1180 can have other rounded or polygonal shapes.

11 is a top perspective view of another example of a capillary array assembly 1300 according to the present disclosure. FIG. 12 is a top exploded perspective view of the capillary array assembly 1300. The capillary array assembly 1300 may have many features that are the same as or similar to the capillary array assembly 1100 shown in FIGS. 9 and 10. Accordingly, such features are indicated by the same reference numerals in FIGS. 11 and 12. In one aspect, the capillary array assembly 1300 differs in that it has a greater number of capillaries 108 (in this example, 96 capillaries 108). In one example, and as shown in FIGS. 11 and 12, the capillary array assembly 1300 has a modular configuration assembled from multiple individual capillary array assemblies 1100 arranged in parallel. Thus, the capillary window holder of the capillary array assembly 1300 can be constructed from a plurality of capillary window holders 1104, which can be configured as described above and shown in Figures 9 and 10.

To facilitate assembly and alignment of the individual capillary array assemblies 1100, the capillary array assembly 1300 may include a bottom plate (or base plate, or bottom cover) 1302 and a top plate (or top wall, or covering) 1306. The individual capillary array assemblies 1100 are placed (sandwiched) between the bottom plate 1302 and the top plate 1306. The bottom plate 1302 includes a plurality of (second) mounting mechanisms 1410 configured to engage with corresponding (first) mounting mechanisms 1180 of the individual capillary array assemblies 1100. In this example, and as best shown in FIG. 10 , the mounting features 1180 are semicircular recesses, where the mounting features 1410 on the bottom plate 1302 may be cylindrical posts configured (e.g., sized and shaped) to complementarily engage (e.g., mate) with the semicircular mounting features 1180 on the capillary array assembly 1100. As is evident from FIG. 10 , when two capillary array assemblies 1100 are positioned adjacent to one another (side by side), corresponding adjacent pairs of the semicircular mounting features 1180 form circular holes into which the post-shaped mounting features 1410 on the bottom plate 1302 mate.

11 and 12, the top plate 1306 may include a transparent portion 1314 covering (directly above) the window portion(s) 1136, and an opaque portion 1318 covering the first end portion(s) 1128 and the second end portion(s) 1132, respectively, thereby functioning as an optical slit. The length of the transparent portion 1314 may be coextensive (equal to or substantially equal to) the length of the capillary window of the capillary 108 at the window portion(s) 1136. The opaque portion 1318 covers the coated portion of the capillary 108 directly adjacent to the capillary window, which may be advantageous, as described above in connection with the example shown in FIGS. 1-6.

To assemble the capillary array assembly 1300, the smaller capillary array assemblies 1100 can be placed side-by-side onto (or into) the bottom plate 1302, utilizing the mounting mechanisms 1410 to properly position and position the capillary array assemblies 1100 relative to one another. Thus, the majority of the mounting mechanisms 1410 fit into holes formed by corresponding pairs of mounting mechanisms 1180, while the mounting mechanisms 1410 at the lateral ends of the bottom plate 1302 fit into recesses (semicircular spaces in this example) in one corresponding mounting mechanism 1180. The top plate 1306 is then placed above the capillary array assembly 1100. Depending on the embodiment, the top plate 1306 may or may not contact the capillary array assembly 1100 and/or the bottom plate 1302. Depending on the embodiment, the top plate 1306 may or may not be fixed or attached to the capillary array assembly 1100 and/or the bottom plate 1302. Fixation or attachment may be mechanical or adhesive in any suitable manner.

Any of the capillary array assemblies disclosed herein can be configured to include a bottom plate and/or a top plate similar to bottom plate 1302 and/or top plate 1306 just described and shown in Figures 11 and 12.

Figure 13 is a top perspective view of another example of a capillary window holder 1504 according to the present disclosure. Figure 14 is a plan view of the capillary window holder 1504. As in other embodiments, the capillary window holder 1504 includes multiple capillary channels configured to hold multiple corresponding capillaries 108 (see Figure 15) such that at least the capillary windows 148 of the capillaries 108 are secured in place in a parallel configuration to reduce or prevent crosstalk between adjacent capillary windows 148. In the illustrated example, twelve capillary channels are provided for twelve capillaries 108, although the capillary window holder 1504 may include any number of capillary channels for a corresponding number of capillaries 108.

As in other embodiments, the capillary array window holder 1504 (i.e., its body) generally includes a top side 1512 and a bottom side 1516 in the x-y plane, a first end 1520, and a second end 1524 axially opposite the first end 1520 along the longitudinal axis (x-axis). The capillary array window holder 1504 (i.e., its body) also includes a window portion 1536. The structure of the capillary array window holder 1504 can also be considered to include a first end portion 1528 terminating at the first end 1520, a second end portion 1532 terminating at the second end 1524, with the window portion 1536 disposed along the longitudinal axis between the first end portion 1528 and the second end portion 1532.

In this example, a portion of the capillary array window holder 1504 is configured as a grid of bars or ribs. The grid includes a plurality of longitudinal bars arranged parallel to the longitudinal axis and spaced apart from one another along the transverse axis, and at least two transverse bars (e.g., a first transverse bar 1522 and a second transverse bar 1526) extending along the transverse axis and spaced apart from one another along the longitudinal axis. The transverse bars 1522 and 1526 divide each longitudinal bar into axially elongated window bars 1556 axially disposed between corresponding first and second end bars 1566 and 1574. Depending on the embodiment, the transverse bars 1522 and 1526 may also be required to provide structural support for the longitudinal bars and/or simplify the manufacturing process of the capillary array window holder 1504.

The transverse bars 1522 and 1526 define the axial ends of the window portion 1536. Thus, as in other embodiments, the capillary channels are defined in the window portion 1536 by individual open channels 1578, which are separated by axially elongated window bars 1556. At least the window bars 1556 (or more preferably the entire capillary array window holder 1504) are made of an opaque material to reduce or eliminate capillary crosstalk, as described above.

In this example, the capillary array assembly 1500 has a pass-through-illumination configuration, which allows light to pass through the window portion 1536 on both the top side 1504 and the bottom side 1516. Because of this, both the top side 1504 and the bottom side 1516 are open (at least at the window portion 1536) as shown. That is, the open channel 1578 is not covered by the top or bottom walls.

Also, as shown in Figures 13 and 14, the capillary array window holder 1504 may include a mounting mechanism 1580 similar to the mounting mechanism 1180 described above in connection with Figures 9 and 10. Thus, several capillary array window holders 1504 may be arranged in parallel as modules or parts of a larger capillary array assembly, similar to the capillary array assembly 1300 described above and shown in Figures 11 and 12.

15 is a longitudinal side view of another example of a capillary array assembly 1700 according to the present disclosure, which includes a capillary array window holder 1504 and a plurality of capillaries 108 disposed in the capillary array window holder 1504. In this example, the capillaries 108 are positioned in the capillary array window holder 1504 such that at least their capillary windows 148 are disposed in a parallel, interlocking relationship with the window bar 1556. Thus, with this configuration, the capillary windows 148 are optically blocked in the lateral direction (perpendicular to the drawing sheet) by the window bar 1556, as in other embodiments disclosed herein. In the illustrated example, this configuration is achieved by the capillaries 108 being bent over or under the transverse bars 1522 and 1526 (or, in the particularly illustrated example, bent over one transverse bar 1522 and under the other transverse bar 1526), with the portions of the capillaries 108 containing the capillary windows 148 being fully contained within the corresponding open channels 1578. The capillary array assembly 1700 may include bottom and/or top plates (not shown) as needed to hold the capillaries 108 within the capillary array window holder 1504, as shown in FIG. 15. For example, the bottom plate 1302 and/or top plate 1306 described above and shown in FIGS. 11 and 12 may be configured (i.e., adapted, modified, etc.) for this purpose.

FIG. 16 is a schematic diagram of an example sample analysis system (or apparatus, analytical instrument, etc.) 1800 including one or more capillary array assemblies 100 (or 700, or 800, etc.) according to any of the examples described herein. The sample analysis system 1800 is configured to perform optical measurements on samples within the capillaries 108, such as chemical compounds, biological compounds, biological cells or components thereof. In the context of the present disclosure, the term "optical measurements" includes imaging (e.g., microscopic imaging), depending on the type of sample analysis system 1800. In various examples, optical measurements may be based on fluorescence, absorbance, luminescence (including chemiluminescence or bioluminescence), (UV, visible, or IR) spectroscopy, Raman scattering, microscopy, etc. In general, the structure and operation of various components provided in an optical sample analysis instrument will be understood by those skilled in the art and will only be briefly described herein to facilitate understanding of the present disclosure.

The capillary array assembly 100 is configured to be loaded into an operating position within the sample analysis system 1800 so that the capillary windows supported by the capillary array assembly 100 are in precise optical relationship with the optical system of the sample analysis system 1800. The optical system includes one or more photodetectors (or cameras) 1802 configured to receive and measure emission light EM emitted from the exposed (optically readable) portions of the capillary array assembly 100. Examples of photodetectors 1802 include, but are not limited to, cameras, photomultiplier tubes (PMTs), photodiodes (PDs), charge-coupled devices (CCDs), active pixel sensors (APSs) such as complementary metal-oxide semiconductor (CMOS) devices, and the like, which are sensitive to the emission wavelengths to be detected.

In some examples (depending on the type of sample analysis system 1800), the optical system further includes one or more light sources 1806 configured to irradiate the samples in the capillaries 108 at the exposed portions of the capillary array assembly 100 by transmitting excitation light EX at a selected wavelength(s). Examples of light sources 1806 include, but are not limited to, broadband light sources (e.g., flash lamps), light-emitting diodes (LEDs), laser diodes (LDs), lasers, etc. Multiple light sources 1806 may be provided to allow a user to select a desired excitation wavelength.

The optical system may further include various types of emission optics 1810 configured to transmit emission light EM from the capillary array assembly 100 to the photodetector 1804, or additional excitation optics 1814 configured to transmit excitation light EX from the light source 1806 to the capillary array assembly 100. Examples of emission optics 1810 or excitation optics 1814 include, but are not limited to (as needed and as would be understood by one of ordinary skill in the art), lenses, readheads, apertures, optical filters, light guides, mirrors, beam splitters, beam steering devices, monochromators, diffraction gratings, prisms, optical path switches, etc.

The capillary array assembly 100 and optical system are disposed within an instrument console (or device housing, enclosure, etc.) 1818 configured to prevent stray light from reaching the capillaries 108. The instrument console 1818 also provides an enclosed environment to allow environmental control (e.g., temperature control) within the console, if desired. The instrument console 1818 may also house various other components of the sample analysis system 1800 described herein. The instrument console 1818 may include one or more panels, doors, drawers, etc. for loading/removing the capillary array assembly 100 and other portable/replaceable components to provide access to the interior areas and components of the sample analysis system 1800.

In one example, the sample analysis system 1800 includes a sample source 1822 positioned upstream of the capillary array assembly 100. Generally, the sample source 1822 is any component or group of components configured to provide a sample that can be introduced into or loaded into the individual capillaries 108. To this end, the inlet end 1826 of each capillary 108 may be in fluid communication with the sample source 1822, either directly or via other fluid components (e.g., tubing, fittings, valves, etc.). In one example, one or more components of the sample source 1822 may be manually or (semi-)automatically movable (via doors, drawers, etc.) into and out of the instrument console 1818, as indicated by arrow 1830 in FIG. 16 . In one example, sample source 1822 may be or include one or more containers configured to hold samples, such as a multi-well plate (e.g., a microtiter plate), tubes, vials, cuvettes, etc. Each well (or other type of container) may contain an individual sample and be in fluid communication with a corresponding one of capillaries 108. Each sample may be the same or different from the other samples, for example, in terms of composition and/or conditioning or pretreatment state. In one example, the sample provided by sample source 1822 may originate from another analytical instrument (e.g., an LC instrument or a GC instrument), which may optionally be located upstream of sample analysis system 1800 and fluidly coupled to sample source 1822.

In another example, sample may be pre-loaded into the capillaries 108 before the capillary array assembly 100 is installed in the sample analysis system 1800 and an analysis is performed. In this case, all or part of the sample source 1822 may not be required.

In one example, the sample analysis system 1800 further includes a fluid source 1834. Depending on the type of sample analysis system 1800, the fluid source 1834 may refer to one or more fluid sources configured to supply one or more types of fluid (e.g., solvent, buffer solution, wash/rinse solution, reagent solution, carrier gas, etc.) to the capillary 108. The inlet end 1826 of the capillary 108 may be positioned to be in selective fluid communication with the sample source 1822 and the fluid source 1834 manually or (semi-)automatically depending on the type of sample analysis system 1800.

In examples involving fluid flow through the capillaries 108, the sample analysis system 1800 further includes a receiver 1838 positioned downstream from the capillary array assembly 100. Generally, the receiver 1838 is any suitably configured destination location for receiving the sample after analysis has been performed in the capillary array assembly 100, and any other material that flows through the capillaries 108. To this end, the outlet end 1842 of each capillary 108 may be in fluid communication with the receiver 1838, either directly or via other fluid components (e.g., tubing, fittings, valves, etc.). In one example, the receiver 1838 may be or include one or more containers (e.g., wastewater reservoirs) configured to collect the sample or other material from the capillaries 108. In one example, the sample received by receiver 1838 may then be introduced into another analytical instrument (e.g., an LC or GC instrument, a mass spectrometer, an ion mobility spectrometer, etc.), which may optionally be located downstream from sample analysis system 1800 and fluidly coupled to receiver 1838.

In one example, the sample analysis system 1800 further includes a system controller 1846. The system controller 1846 generally refers to one or more electronic-circuit-based (e.g., computing) devices or modules including various types of hardware (e.g., electronic-circuit-based processors, memory, non-transitory computer-readable media, etc.), firmware (e.g., integrated circuits or ICs), and/or software configured to perform the various functions necessary to operate a sample analysis system 1800 of the type provided. The system controller 1846 may be embodied as one or more types of hardware, such as a circuit board. The system controller 1846 may include a data acquisition circuit (DAC) configured to receive and process signals output from the photodetector 1802 and generate user-interpretable data therefrom representing the results of the sample analysis. The system controller 1846 may also be considered to refer to a device configured to control, monitor, and synchronize the operation of the various components of the sample analysis system 1800, such as the photodetector 1802, the emission optics 1810, the light source 1806, the excitation optics 1814, the sample source 1822, the fluid source 1834, and the receiver 1838. The system controller 1846 may also be considered to refer to user input and output devices, such as a keyboard, a display monitor, a printer, a graphical user interface (GUI), etc. The system controller 1846 may include an operating system (e.g., Microsoft Windows software) for controlling and operating the various functions of the system controller 1846. In one example, the system controller 1846 is configured to control or perform all or a portion of any of the methods disclosed herein. For all such purposes, the system controller 1846 may communicate with the aforementioned components via wired or wireless communication links that enable the transmission of signals (e.g., sending control signals, receiving measurement or feedback signals, etc.).

An example of a general method specifically involving the use of the capillary array assembly 100 for analyzing a sample will now be described. The capillary array assembly 100 containing the sample is prepared. In this example, preparing the capillary array assembly 100 involves loading the capillary array assembly 100 into an operating position within the sample analysis system 1800 to place the capillary array assembly 100 in the correct optical relationship with the optical system of the sample analysis system 1800. In methods involving fluid flow through the capillaries 108, preparing the capillary array assembly 100 also involves placing the capillaries 108 in fluid communication with the sample source 1822 (or, if desired, the fluid source 1834) and the receiver 1838. In some examples of the method, preparing the capillary array assembly 100 also involves introducing sample into individual capillaries 108 by flowing the sample from a sample source 1822 into the capillaries 108 until the sample is located within the capillary window and is therefore accessible by the optical system. As will be appreciated by those skilled in the art, depending on the type of sample analysis being performed, the sample may undergo various types of pretreatment or conditioning (incubation, mixing, homogenization, centrifugation, buffering, reagent addition, etc.) before being placed within the capillary window.

After preparing the capillary array assembly 100 as just described, the method includes performing an optical measurement of a detectable sample at (e.g., located at) the sample window to obtain optical data from one or more analytes of the sample. In a typical example, performing the optical measurement entails irradiating the sample with excitation light EX and collecting the resulting emission light EM emitted from the sample in response to the irradiation. In this example, the optical system of the sample analysis system 1800 described above operates to perform the optical measurement. In some examples, the excitation light EX induces a fluorescent response in one or more analytes of the sample, and the optical measurement involves measuring the intensity of the fluorescence to quantify (e.g., determine the concentration of) the analyte(s) or to further generate an image of the sample containing the fluorescent analyte(s). In other examples, excitation light EX is used to illuminate a sample without necessarily inducing fluorescence, and emission light EM is used to measure the absorbance of the sample to quantify the analyte(s) or to further generate an image of the sample.

In other examples, performing optical measurements does not require irradiating the sample with excitation light EX. As will be understood by one of ordinary skill in the art, for example, sample source 1822 or fluid source 1834 may be configured to add a reagent to the sample that induces luminescence, such as flash luminescence or glow luminescence. As a further example, sample source 1822 or fluid source 1834 may be configured to add a label, such as a stable label or a radioactive label, to the sample, depending on the type of optical measurement being performed.

In all such cases, the emission optics 1810 of the optical system of the sample analysis system 1800 may operate to collect emission light EM from the sample and transmit the emission light EM to the photodetector 1802. The emission light EM may be detected on the same side of the capillary array assembly 100 as the excitation light EX is incident (e.g., the top side), or on the opposite side (e.g., excitation occurs on the top side, but detection occurs on the bottom side). The photodetector 1802 then converts the emission light EM into an electrical signal (detection signal or measurement signal) and transmits the electrical signal to signal processing circuitry, such as the data acquisition circuitry of the system controller 1846 described above.

16 , in one non-exclusive example, the sample analysis system 1800 is configured as a capillary electrophoresis (CE) system. In this case, the capillaries 108 contain an electrophoretic separation medium (i.e., an analytical separation medium prepared for CE) at least at the location of the capillary window. In this example, the electrophoretic separation medium is an electrophoretic polymer gel, which may be a polymer prepared for CE. In this example, the sample analysis system 1800 includes an analytical separation medium source 1850 through which the analytical separation medium can be introduced into the individual capillaries 108. In a particular example, the analytical separation medium source 1850 is an electrophoretic separation medium source, or more specifically, an electrophoretic gel source. The electrophoretic gel source may refer to one or more containers (e.g., reservoirs, bottles, etc.) and components (e.g., pumps, valves, etc.) configured to supply gel to the capillary window by flowing the gel through the capillaries 108 to a waste container in the receiver 1838. The inlet end 1826 of the capillary 108 can be manually or (semi-)automatically placed in selective fluid communication with the analytical separation medium source 1850 (and can be switched between the analytical separation medium source 1850, the sample source 1822, and the fluid source 1834 as needed), depending on the embodiment of the sample analysis system 1800. In other examples, the capillary 108 is pre-filled with gel (or other type of analytical separation medium), in which case the analytical separation medium source 1850 is not required. In other examples, another type of analytical separation medium, such as, for example, a chromatographic separation medium, can be utilized.

In the example of a CE system, the sample analysis system 1800 further includes a high voltage (HV) power supply configured to apply a potential difference across the length of each of the capillaries 108 (i.e., between their input end 1826 and output end 1842). The HV power supply includes a voltage source 1854 electrically coupled by wiring to one or more input electrodes 1858 (e.g., cathodes) and one or more output electrodes 1862 (e.g., anodes). For example, the input electrode(s) 1858 may be submerged within the cathode reservoir of the sample source 1822 so as to be electrically coupled to the capillaries 108 (particularly the sample and associated fluids within the capillaries 108) via the electrolyte in the cathode reservoir. As a further example, a pair of capillary inlet ends 1826 and input electrodes 1858 may be submerged in each well of a multiwell plate into which individual samples are delivered. Similarly, output electrode(s) 1862 may be submerged in the anode reservoir of receiver 1838 so as to be electrically coupled to capillary 108 (particularly the sample and associated fluids within capillary 108) via the electrolyte within the anode reservoir. As will be understood by those skilled in the art, voltage source 1854 refers to the various components (e.g., waveform generator, amplifier, etc.) necessary to apply a potential difference having the desired operating parameters (amplitude/magnitude, frequency, waveform(s), pulse rate, etc.) to perform CE.

Another example of a method for analyzing a sample will now be described, particularly in the context of CE. The method may generally include preparing a capillary array assembly 100 and then performing an optical measurement of a sample within a sample window to obtain optical data from one or more analytes of the sample. If the capillaries 108 are not pre-filled with an electrophoretic separation medium, the method includes supplying an electrophoretic separation medium to the capillaries 108 before supplying the sample to the capillaries 108 and before performing the optical measurement, as described above. In this example, the method further includes applying a potential difference (typically simultaneously, in parallel) across the capillaries 108 before and/or during the optical measurement. The potential difference induces different analytes to migrate through the electrophoretic separation medium at different rates depending on their different size and/or charge states, according to mechanisms commonly understood by those skilled in the art. In this manner, the different analytes are separated from one another, thereby facilitating optical measurement of one or more target analytes of interest within the sample.

Exemplary embodiment

Exemplary embodiments provided in accordance with the present disclosure include, but are not limited to, the following:

1. A capillary array window holder comprising: a first end portion; a second end portion; and a window portion disposed along a longitudinal axis between the first end portion and the second end portion; the window portion including a plurality of window bars extending along the longitudinal axis and spaced apart from one another along a transverse axis perpendicular to the longitudinal axis; the window bars defining a plurality of parallel open channels configured to respectively accommodate a plurality of capillaries, the window bars being made of an opaque material such that the window bars block line of sight along the transverse axis between adjacent open channels; the open channels being exposed at an upper side of the window portion to allow transmission of light to and from the open channels at the upper side.

2. The capillary array window holder of embodiment 1, wherein at least one of the first end portion or the second end portion includes an attachment mechanism configured to engage a structure to attach the capillary array window holder to the structure.

3. The capillary array window holder of embodiment 2, wherein the window portion is positioned in a capillary plane, and the mounting mechanism includes a plate positioned in a mounting plane spaced apart from the capillary plane along a height axis perpendicular to the longitudinal axis and perpendicular to the horizontal axis.

4. The capillary array window holder of embodiment 2 or 3, wherein the attachment mechanism includes a recess configured to engage a post.

5. The capillary array window holder of any one of embodiments 1 to 4, wherein the first end portion includes a plurality of first end bars defining a plurality of first end channels aligned with the open channels along the longitudinal axis, and the second end portion includes a plurality of second end bars defining a plurality of second end channels aligned with the open channels along the longitudinal axis.

6. A capillary array window holder as described in embodiment 5, wherein the first end portion includes a first upper wall covering the first end channel on the upper side, and the second end portion includes a second upper wall covering the second end channel on the upper side.

7. A capillary array window holder according to any one of embodiments 1 to 6, wherein the central portion includes a bottom wall located on the bottom side of the capillary array window holder opposite the upper side, the bottom wall covering the open channel on the bottom side.

8. A capillary array window holder according to any one of embodiments 1 to 6, wherein the open channel has a central portion exposed on a bottom side of the capillary array window holder opposite the top side, such that light can pass from the top side through the open channel to the bottom side.

9. A capillary array window holder as described in any one of embodiments 1 to 8, wherein each window bar has a cross-section in a front surface perpendicular to the longitudinal axis, the cross-section being defined by a bar width and a bar height, the cross-section having a bar height to bar width ratio in the range of 1 to 10.

10. A capillary array window holder according to any one of embodiments 1 to 9, wherein each window bar has a cross section in a front surface perpendicular to the longitudinal axis, the cross section being defined by a bar width and a bar height, the bar width being in the range of 20 μm to 200 μm, and the bar height being in the range of 100 μm to 400 μm.

11. A capillary array window holder according to any one of embodiments 1 to 10, wherein each open channel has a cross section in a front surface perpendicular to the longitudinal axis, the cross section being configured as a straight line.

12. A capillary array window holder according to any one of embodiments 1 to 11, wherein each open channel has a cross section in a front surface perpendicular to the longitudinal axis, and at least a bottom portion of the cross section is at least partially V-shaped.

13. A capillary array window holder according to any one of embodiments 1 to 12, wherein the opaque material is opaque to light propagating in a wavelength range of 190 nm to 800 nm.

14. The capillary array window holder of any one of embodiments 1 to 13, wherein the window bar is made of a material selected from the group consisting of metal; aluminum; nickel; copper; metal alloy; silicon; ceramic; glass; polymer; plastic; polyoxymethylene (POM); liquid crystal polymer (LCP); polyacrylamide (PA); polycarbonate (PC); polymethyl methacrylate (PMMA); polyether ether ketone (PEEK); and polyethylene (PE).

15. A capillary array assembly comprising: a capillary array window holder according to any one of embodiments 1 to 14; and a plurality of capillaries, each capillary positioned in a respective one of the capillary channels such that the window of each capillary is positioned in the respective open channel.

16. The capillary array assembly of embodiment 15, wherein each of the window bars has a bar height in a front surface perpendicular to the longitudinal axis, the bar height being equal to or greater than the outer diameter of the capillary in the window portion.

17. The capillary array assembly of embodiment 15 or 16, wherein each of the capillaries has an outer diameter of less than 1 mm at the window portion.

18. The capillary array assembly of any one of embodiments 15 to 17, further comprising a top plate disposed on or above the capillaries on the upper side, wherein at least a portion of the top plate covering the window portion is transparent.

19. The capillary array assembly of any one of embodiments 15 to 18, wherein at least one of the first end portion or the second end portion includes a first attachment mechanism and further includes a bottom plate on the bottom side, the bottom plate including a second attachment mechanism that engages with the first attachment mechanism.

20. A capillary array assembly comprising: a plurality of capillary array window holders according to any one of embodiments 1 to 14 arranged side by side along the horizontal axis; and a plurality of capillaries, each capillary positioned in a respective one of the capillary channels in each capillary array window holder such that the window of each capillary is positioned in the respective open channel.

21. The capillary array assembly of embodiment 20, wherein at least one of the first end portion or the second end portion of each capillary array window holder includes a first attachment mechanism and further includes a bottom plate on the bottom side, the bottom plate including a plurality of second attachment mechanisms, each of which engages with one or more of the first attachment mechanisms.

22. A sample analysis system comprising: a capillary array assembly described in any one of embodiments 15 to 21; and a photodetector disposed in an optical relationship with the open channel.

23. The sample analysis system of embodiment 22, further comprising a light source disposed in optical relationship with the open channel.

24. The sample analysis system of embodiment 22 or 23, comprising a sample source through which a sample can be introduced into the capillary.

25. The sample analysis system of any one of embodiments 22 to 24, comprising a voltage source in electrical communication with the capillary and configured to apply a potential difference across the capillary effective to perform capillary electrophoresis on a sample in the capillary.

26. The sample analysis system of any one of embodiments 22 to 25, further comprising an analytical separation medium source through which an analytical separation medium can be introduced into the capillary.

27. The sample analysis system of embodiment 26, wherein the analytical separation medium comprises an electrophoretic separation medium.

28. A method for analyzing a sample, the method comprising: providing a capillary array assembly including: a plurality of open channels exposed to light on at least an upper side of the capillary array assembly, adjacent open channels separated from one another by window bars made of opaque material; and a plurality of capillaries including individual windows disposed within the open channels, the window bars blocking line of sight between adjacent windows; and performing optical measurements of detectable samples at the windows to obtain optical data from one or more analytes of the sample.

29. The method of embodiment 28, wherein performing the optical measurement includes detecting emitted light emitted from the window.

30. The method of embodiment 28 or 29, wherein the detection occurs on the upper side.

31. The method of embodiment 28 or 29, wherein the detection occurs on the bottom side of the capillary array assembly, opposite the top side.

32. The method of any one of embodiments 28 to 31, wherein performing the optical measurement includes irradiating the sample with excitation light.

33. The method of embodiment 28 or 29, wherein performing the optical measurement includes illuminating the sample with excitation light and detecting emission light emitted from the window, and both the illumination and the detection occur on the top side.

34. The method of embodiment 28 or 29, wherein performing the optical measurement includes illuminating the sample with excitation light and detecting emission light emitted from the window, the illumination occurring at the top side and the detection occurring at the bottom side of the capillary array assembly opposite the top side.

35. The method of any one of embodiments 28 to 34, comprising flowing the sample into a capillary.

36. The method of any one of embodiments 28 to 35, comprising analytically separating the sample in each capillary before and/or during the optical measurements.

37. The method of embodiment 36, wherein analytically separating the sample comprises subjecting the sample to capillary electrophoresis.

38. The method of any one of embodiments 28 to 37, comprising flowing the analytical separation medium into a capillary.

39. The method of embodiment 38, wherein the analytical separation medium comprises an electrophoretic separation medium.

As will be understood, terms such as "communicate" and "in communication" (e.g., a first component "communicates" or "communicates" with a second component) are used herein to indicate a structural, functional, mechanical, electrical, signal, optical, magnetic, electromagnetic, ionic, or fluid relationship between two or more components or elements. As such, the fact that one component is said to communicate (communicate) with a second component is not intended to exclude the possibility that additional components may be present between the first and second components and/or operatively associated with or involved in the first and second components.

As will be understood, various aspects or details of the present invention may be changed without departing from the scope of the present invention. Moreover, the above description is by way of example only, and not by way of limitation, and the present invention is defined by the following claims.

Claims (18)

a first end portion; and
a second end portion; and
a window portion disposed along a longitudinal axis between the first end portion and the second end portion, the window portion including a plurality of window bars extending along the longitudinal axis and spaced apart from one another along a transverse axis perpendicular to the longitudinal axis;
the window bar defines a plurality of parallel open channels configured to receive a plurality of capillaries, each of the parallel open channels being made of an opaque material such that the window bar blocks propagation of light along the transverse axis between adjacent open channels;
the open channel is exposed at the top side to allow transmission of light to and from the open channel above the window portion ;
the first end portion includes a plurality of first end bars defining a plurality of first end channels aligned with the open channels along the longitudinal axis, and the second end portion includes a plurality of second end bars defining a plurality of second end channels aligned with the open channels along the longitudinal axis;
A capillary array window holder, wherein the first end portion includes a first upper wall covering the first end channel on the upper side, and the second end portion includes a second upper wall covering the second end channel on the upper side . at least one of the first end portion or the second end portion includes an attachment mechanism configured to engage a structure to attach the capillary array window holder to the structure;
2. The capillary array window holder of claim 1, wherein at least one of the first end portion or the second end portion includes an attachment mechanism configured to engage with a structure to attach the capillary array window holder to the structure, the window portion being located in a capillary plane, and the attachment mechanism including a plate located in an attachment plane spaced apart from the capillary plane along a height axis perpendicular to the longitudinal axis and perpendicular to the horizontal axis. A capillary array window holder as described in claim 1 or 2, wherein the window portion includes a bottom wall located on the bottom side of the capillary array window holder opposite the upper side, and the bottom wall covers the open channel on the bottom side. 3. A capillary array window holder as described in claim 1 or 2, wherein the open channel is exposed to the bottom side so as to allow the window portion to transmit light from the top side through the open channel to the bottom side of the capillary array window holder opposite the top side. 5. A capillary array window holder as claimed in any one of claims 1 to 4, wherein each window bar has a cross section in a front surface perpendicular to the longitudinal axis, the cross section being defined by a bar width and a bar height, the cross section having a bar height to bar width ratio in the range of 1 to 10 . A capillary array window holder as described in any one of claims 1 to 4, wherein each window bar has a cross section in a front surface perpendicular to the longitudinal axis, the cross section being defined by a bar width and a bar height, the bar width being in the range of 20 μm to 200 μm, and the bar height being in the range of 100 μm to 400 μm. A capillary array window holder according to any one of claims 1 to 6 , wherein each open channel has a cross section in a front surface perpendicular to the longitudinal axis, the cross section being configured as a straight line. 8. A capillary array window holder according to claim 1 , wherein the opaque material is opaque to light propagating in the wavelength range of 190 nm to 800 nm. The capillary array window holder of any one of claims 1 to 7, wherein the window bar is made of a material selected from the group consisting of metal; aluminum; nickel; copper; metal alloy; silicon; ceramic; glass; polymer; plastic; polyoxymethylene (POM); liquid crystal polymer (LCP); polyacrylamide (PA); polycarbonate (PC); polymethyl methacrylate (PMMA); polyether ether ketone (PEEK); and polyethylene (PE). 1. A capillary array assembly comprising:
a capillary array window holder according to claim 1 or 2 ;
a plurality of capillaries, each capillary positioned in a respective one of said open channels such that a window of each capillary is positioned in said open channel. The capillary array assembly of claim 10 , wherein each of the window bars has a bar height in a front surface perpendicular to the longitudinal axis, the bar height being equal to or greater than the outer diameter of the capillary in the window portion. 12. The capillary array assembly according to claim 10 or 11, comprising an upper plate arranged on or above the capillaries on the upper side, at least a portion of the upper plate covering the window portion being transparent. 1. A capillary array assembly comprising:
a plurality of capillary array window holders according to claim 1 or 2 arranged side by side along the horizontal axis;
a plurality of capillaries, each capillary positioned in a respective one of said open channels in each capillary array window holder such that a window of each capillary is positioned in said respective open channel. 1. A sample analysis system comprising:
A capillary array assembly according to any one of claims 10 to 13 ;
a photodetector disposed in optical relationship with the open channel; a light source disposed in optical relationship with said open channel;
a sample source from which a sample can be introduced into said capillary;
a voltage source in electrical communication with the capillary and configured to apply a potential difference across the capillary effective to perform capillary electrophoresis on a sample in the capillary;
an analytical separation medium source by which an analytical separation medium can be introduced into said capillary;
15. The sample analysis system of claim 14 , comprising at least one analytical separation medium source from which an analytical separation medium can be introduced into said capillary, said analytical separation medium comprising an electrophoretic separation medium. 1. A method for analyzing a sample, comprising:
providing the capillary array assembly according to any one of claims 10 to 13 ;
performing optical measurements of each detectable sample at said window to obtain optical data from one or more analytes of the sample. performing the optical measurement
detecting emitted light from the window, the detection occurring at the top side;
detecting emitted light from the window, the detection occurring on a bottom side of the capillary array assembly opposite the top side;
illuminating the sample with excitation light and detecting emission light emitted from said window, said illumination and said detection both occurring at said top side;
17. The method of claim 16, comprising one of illuminating a sample with excitation light and detecting emission light emitted from the window, the illumination occurring at the top side and the detection occurring at a bottom side of the capillary array assembly opposite the top side. allowing the sample to flow into the capillary;
analytically separating the sample in each capillary before and/or during said optical measurements;
analytically separating a sample in each capillary before and/or during said optical measurements, wherein analytically separating the sample comprises subjecting the sample to capillary electrophoresis;
flowing an analytical separation medium into the capillary;
18. The method of claim 16 or 17 , comprising at least one of: flowing an analytical separation medium into the capillary; and wherein the analytical separation medium comprises an electrophoretic separation medium.